An emerging set of molecular and nanotechnologies are being developed that promise to revolutionize pathologic analysis of cancer samples. Microfluidics integrated nanoelectronic sensors facilitate the separation, manipulation, and multi-parameter measurement of genes and proteins in large numbers of cancer cells from tissue sample, thus providing a more complete characterization of its pathologic state, including intratumor molecular heterogeneity. These technologies have the potential to rapidly and reproducibly identify predictive molecular signatures that can be used to guide patient therapy. Although technical challenges remain, these technologies are now ready to be tested in biologically and clinically relevant cancer models. The UCLA/CalTech/Fluidigm team is an international leader in the development of microfluidics integrated nanoelectronic sensors. The UCLA pathology team has recently identified a predictive molecular signature that is significantly, and reproducibly, associated with glioblastoma patient response to EGFR kinase inhibitor therapy. Taking advantage of this synergy between technological and clinical expertise, this proposal will optimize and validate microfluidics integrated nanoelectronic sensors as a diagnostic tool for cancer. In aim 1, preparation of human glioblastoma patient samples will be optimized, intratumor molecular heterogeneity in clinical samples will be measured, and the ability of microfluidic integrated nanoelectronic sensors to perform multiparameter measurements of single cancer cells in tumor tissue will be validated. In aim 2, the utility of microfluidics integrated nanoelectronic sensors to guide therapy decisions will be determined. In aim 3, new materials for improved multiparameter quantitative analysis of cancer cells using microfluidics integrated nanoelectronic sensors will be developed and validated.